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α-Hederin Increases The Apoptosis Of Cisplatin-Resistant Gastric Cancer Cells By Activating Mitochondrial Pathway In Vivo And Vitro

α-Hederin Increases The Apoptosis Of Cisplatin-Resistant Gastric Cancer Cells By Activating Mitochondrial Pathway In Vivo And Vitro

Yinghui Liu, Hongbo Lei, Jingjing Ma, Huan Deng, Pengzhan He, Weiguo Dong

Onco Targets Ther. 2019 Oct 23;12:8737-8750.

PMID: 31695431

Abstract:

Introduction:
Gastric cancer remains an important cancer worldwide, and conventional chemotherapeutic drugs have the defects of drug resistance and cell toxicity. α-Hederin has been found to have certain therapeutic effects on various types of human cancers. However, studies on the α-hederin that exert biological activities on the cisplatin-resistant gastric cancer cells are limited. In this study, we evaluated the effects of α-hederin in HGC27/DDP and the potential mechanisms both in vivo and in vitro.
Methods:
HGC27/DDP cells were cultured in DMEM/F12 medium. Cell proliferation and viability were assessed quantitatively using Cell Counting Kit-8. Cell invasion and migration were detected by Transwell invasion assay and wound healing assay. Cell apoptosis was examined by employing Hoechst 33258 Staining Kit and an Annexin V-PE apoptosis kit. Intracellular GSH levels were examined by using a GSH Assay Kit. DCFH-DA and JC-1 Kit were used to detect levels of intracellular reactive oxygen species (ROS) and changes in mitochondrial membrane potential (∆Ψm). The protein levels of Apaf-1, AIF, Bax, Bcl-2, Cyt C, Survivin, cleaved caspase-3, cleaved caspase-9, MMP-9 and MMP-2 were detected by Western blot analysis. The effect of α-hederin in vivo was observed by xenograft tumor models in nude mice.
Results:
The α-hederin treatment significantly inhibited the proliferation in a dose- and time-dependent manner of HGC27/DDP and induced obvious apoptosis compared with the control group (P<0.05). Meanwhile, the ability of cells to invade and migrate was suppressed (P<0.05). The α-hederin induced the depletion of GSH (P<0.05) and the accumulation of intracellular ROS (P<0.05), changed the mitochondrial membrane potential (P<0.05), increased the Bax, Apaf-1, AIF, Cyt C, cleaved caspase-3 and cleaved caspase-9 expression and decreased the protein level of Bcl-2, survivin, MMP-9 and MMP-2 (P<0.05). Pretreatment with NAC (12 mM) enhanced the tendency and pretreatment with BSO (8 mM) attenuated the tendency above (P<0.05). Meanwhile, α-hederin inhibited xenograft tumor growth in vivo (P<0.05).
Conclusion:
Our study provides strong molecular evidence to support our hypothesis that α-hederin inhibits the proliferation and induces the apoptosis of HGC27/DDP cells by increasing the levels of intracellular ROS and triggering mitochondrial pathway activation.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP27013918	α-Hederin		27013-91-8	Price

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